Two new entrants have joined the controversy over whether bone marrow stem cells can heal damaged heart tissue. Studies published this week suggest that when stem cells derived from mouse bone marrow are injected into damaged mouse hearts, the cells remain blood cells and do not become heart tissue.

These negative results are at odds with previous studies in both mice and humans. In 2001, Piero Anversa and his colleagues at New York Medical College in Valhalla, New York, reported that bone marrow stem cells injected into damaged hearts became cardiac cells and improved heart function in 40 percent of treated mice.

And last year a 16-year-old Michigan teen was treated with his own bone marrow stem cells after being shot with a nail gun in his heart. The teen showed substantial improvement and is reportedly leading a normal life.

However, during the same year, three research teams reported that bone marrow stem cells did not become heart cells when injected into damaged mouse hearts, but instead fused with existing heart cells to restore function.

The new studies indicate that the injected bone marrow stem cells do not fuse with existing heart cells and do not differentiate, or turn into, heart cells.

“We set out to reproduce the original experiments showing that heart tissue could regenerate by transferring bone marrow stem cells into damaged regions,” says Charles E. Murry at the University of Washington in Seattle, who led one of the recent studies. “But we could not detect a single cell in the heart that had come from injected cells.”

However, Anversa stands by his original study and notes that “many clinical trials demonstrate beneficial effects in real patients.”

The study by Murry and his colleagues and another study led by Robert C. Robbins of Stanford University in Stanford, California, appear this week in Nature.

The differing results have fueled a controversy over whether such experiments should be conducted on humans and whether heart patients might benefit from bone marrow stem cell therapy. Many researchers say that it is important to understand what happens to bone marrow stem cells when they are injected into ailing hearts before trying the therapy on humans.

But, several clinical trials around the world are reporting marked improvements in heart function in patients treated with their own bone marrow cells.

For example, last fall researchers from the University of Frankfurt in Germany reported that 28 patients who received injections of their own bone marrow progenitor cells showed increases in pumping efficiency and decreases in the amount of dead cardiac tissue compared to patients who did not receive bone marrow cells.

And researchers at the Texas Heart Institute in Houston reported at the American Heart Association’s annual meeting last November that patients in Brazil who received injections of a subset of bone marrow cells experienced significant improvements in heart function.

Other clinical trials in the United Kingdom, Hong Kong, Japan, and Germany have also reported improvements in patients receiving injections of stem cells and progenitor cells derived from bone marrow.

Researchers don’t yet understand why different research groups have come up with such diverse results. Various laboratories have used an assortment of methods to purify and identify bone marrow stem cells. Bone marrow contains a mixture of cells in progressive stages of becoming the diverse types of cells that populate the blood.

While some laboratories work with pure populations of stem cells, other labs may be dealing with mixtures of stem cells and progenitor cells—cells that are in intermediate stages of maturation.

Also, laboratories have used a range of methods to track the injected cells as well as to induce damage in animal models. Injured tissues send out chemical signals to attract stem cells for repair. It is not known if the same signals are at play in each experiment.

Despite so many unanswered questions, many physicians point out that as long as patients are dying, it is important to investigate this approach to treating disease.

“It’s important to move this research forward,” says Steven Timmis of Beaumont Hospital in Royal Oaks, Michigan, who used bone marrow stem cells to treat the injured teenager. “There is enormous demand for answers on these crucially important questions.”